negative regulation of mitochondrial membrane potential

Definition

Target type: biologicalprocess

Any process that stops, prevents, or reduces the frequency, rate or extent of establishment or extent of a mitochondrial membrane potential, the electric potential existing across any mitochondrial membrane arising from charges in the membrane itself and from the charges present in the media on either side of the membrane. [GOC:dph, GOC:tb]

Mitochondrial membrane potential (MMP), the difference in electrical charge across the inner mitochondrial membrane, is a crucial factor in ATP production and cellular function. Negative regulation of MMP involves processes that decrease the electrochemical gradient across the inner mitochondrial membrane, ultimately reducing ATP synthesis. This regulation is essential for maintaining cellular homeostasis, preventing excessive oxidative stress, and responding to various cellular stresses.

Key mechanisms involved in negative regulation of MMP include:

1. **Uncoupling Proteins (UCPs):** These proteins facilitate the dissipation of the proton gradient across the inner mitochondrial membrane, bypassing ATP synthase and reducing ATP production. This process generates heat, playing a role in thermogenesis and protection against oxidative stress.

2. **Inhibition of Electron Transport Chain (ETC):** The ETC is responsible for pumping protons across the inner mitochondrial membrane, generating the proton gradient. Inhibition of ETC complexes, such as by reactive oxygen species (ROS), decreases proton pumping and reduces MMP.

3. **Opening of Mitochondrial Permeability Transition Pore (mPTP):** The mPTP is a large channel in the inner mitochondrial membrane that allows the passage of ions and small molecules. When opened, it dissipates the proton gradient, leading to a rapid decrease in MMP. This can trigger apoptosis or necrosis, depending on the context.

4. **Increased Reactive Oxygen Species (ROS) Production:** ROS can disrupt the electron transport chain, leading to decreased MMP. Additionally, high levels of ROS can directly damage mitochondrial components, contributing to MMP decline.

5. **Calcium Overload:** Excessive calcium influx into mitochondria can disrupt ETC function and promote mPTP opening, decreasing MMP.

6. **Depletion of Mitochondrial Substrate:** Reduced levels of substrates like pyruvate or fatty acids can limit ATP production and decrease MMP.

These processes are tightly regulated, involving complex signaling pathways and interactions between various proteins and metabolites. They play essential roles in cellular adaptation to stress, energy metabolism, and programmed cell death. Disruptions in negative regulation of MMP can lead to various diseases, including cancer, neurodegenerative disorders, and cardiovascular disease. '
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Proteins (4)

Compounds (90)